Human colon tumor-on-a-chip based on magnetic microcontainers encapsulated cancer spheroids

Tumor-on-a-chip platforms are increasingly recognized as promising preclinical tools for developing personalized therapies. However, effectively recapitulating tumor heterogeneity, three-dimensional architecture, and the dynamic in vivo microenvironment remains a significant challenge. Here, we developed magneto-responsive microcontainers for controllable culture of the patient-derived colorectal tumor cells (pCRCs) spheroids. Using microfluidic electrospray technology, microcontainers with a biocompatible carboxymethyl cellulose (CMC) core and a magnetic Fe₃O₄@alginate shell were fabricated for efficient harvest of pCRCs-spheroids. In addition, the microcontainers underwent rotational motion under an external magnetic field, thereby modulating local molecular transport. Moreover, integration of such pCRCs-laden microcontainer into a branched microfluidic chip enabled the generation of drug concentration gradients. Functional on-chip assays revealed heterogeneous drug responses among patient-derived spheroids and enabled preliminary comparison with the available clinical outcomes. Collectively, this magnetic chip-based platform offers a controllable in vitro approach for high-throughput, patient-specific chemotherapy screening in colorectal cancer.